Queer- and trans-inclusive faculty hiring-A call for change.

As queer and trans scientists, we face varied and systemic barriers to our professional success, resulting in our relative absence from faculty ranks at many institutions. In this Perspective, we call for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process.

Effects of therapeutically approved individual bile acids on the development of metabolic dysfunction-associated steatohepatitis a low bile acid mouse model.

Bile acid (BA) signaling dysregulation is an important etiology for the development of metabolic dysfunction-associated steatotic liver disease (MASLD). As diverse signaling molecules synthesized in the liver by pathways initiated with CYP7A1 and CYP27A1, BAs are endogenous modulators of farnesoid x receptor (FXR). FXR activation is crucial in maintaining BA homeostasis, regulating lipid metabolism, and suppressing inflammation.

GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.

Disruptions in circadian rhythms are associated with an increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole body rhythms in metabolism.

Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation.

Macrophages play a key role in ozone-induced lung injury by regulating both the initiation and resolution of inflammation. These distinct activities are mediated by pro-inflammatory and anti-inflammatory/proresolution macrophages which sequentially accumulate in injured tissues. Macrophage activation is dependent, in part, on intracellular metabolism.

Chronic stress and its effects on behavior, RNA expression of the bed nucleus of the stria terminalis, and the M-current of NPY neurons.

Mood disorders, like major depressive disorder, can be precipitated by chronic stress and are more likely to be diagnosed in cisgender women than in cisgender men. This suggests that stress signaling in the brain is sexually dimorphic. We used a chronic variable mild stress paradigm to stress female and male mice for 6 weeks, followed by an assessment of avoidance behavior: the open field test, the elevated plus maze, the light/dark box emergence test, and the novelty suppressed feeding test.

Using Animal Models for Gender-Affirming Hormone Therapy.

We have recently proposed experimental design guidelines and areas of study for preclinical rodent models of gender-affirming hormone therapy in neuroscience. These guidelines also apply to any field subject to the influences of gonadal steroid hormones, including metabolism and growth, cancer, and physiology. This perspective briefly describes our suggestions for these fields.

Intermittent fasting disrupts hippocampal-dependent memory and norepinephrine content in aged male and female mice.

Intermittent fasting (IMF) is associated with many health benefits in animals and humans. Yet, little is known if an IMF diet affects mood and cognitive processing. We have previously identified that IMF in diet-induced obese males increases norepinephrine and dopamine content in the hypothalamus and increases arcuate neuropeptide Y (NPY) gene expression more than in ad libitum control males.

Inflammation-inducible promoters to overexpress immune inhibitory factors by MSCs.

Background: Mesenchymal stromal cells (MSCs) are excessively investigated in the context of inflammation-driven diseases, but the clinical results are often moderate. MSCs are naturally activated by inflammatory signals, which lead to the secretion of immune inhibitory factors in inflamed tissues. Many work groups try to improve the therapeutic outcome of MSCs by genetic modification and the constitutive overexpression of immune modulatory transgenes.

Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors.

Corticotropin-releasing factor (CRF) in the anterior bed nucleus of the stria terminalis (aBNST) is associated with chronic stress and avoidance behavior. However, CRF + BNST neurons project to reward- and motivation-related brain regions, suggesting a potential role in motivated behavior. We used chemogenetics to selectively activate CRF+ aBNST neurons in male and female CRF-ires-Cre mice during an effort-related choice task and a concurrent choice task.

Saturated Fatty Acids and Omega-3 Polyunsaturated Fatty Acids Improve Metabolic Parameters in Ovariectomized Female Mice.

In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17β-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks.

Beyond the Binary: Gender Inclusivity in Schizophrenia Research.

Schizophrenia is a severe neuropsychiatric disorder with significant differences in the incidence and symptomology between cisgender men and women. In recent years, considerably more attention has been on the inclusion of sex and gender in schizophrenia research. However, the majority of this research has failed to consider gender outside of the socially constructed binary of men and women.

The influence of estrogen response element ERα signaling in the control of feeding behaviors in male and female mice.

Circulating 17β-estradiol (E2) controls energy homeostasis and feeding behaviors primarily by its nuclear receptor, estrogen receptor (ER) α. As such, it is important to understand the role of ERα signaling in the neuroendocrine control of feeding. Our previous data indicated that the loss of ERα signaling through estrogen response elements (ERE) alters food intake in a female mouse model.

Perspective on equitable translational studies and clinical support for an unbiased inclusion of the LGBTQIA2S+community.

Research regarding the mental health of the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, 2 Spirit (LGBTQIA2S+) community has been historically biased by individual and structural homophobia, biphobia, and transphobia, resulting in research that does not represent the best quality science. Furthermore, much of this research does not serve the best interests or priorities of LGBTQIA2S + communities, despite significant mental health disparities and great need for quality mental health research and treatments in these populations. Here, we will highlight how bias has resulted in missed opportunities for advancing understanding of mental health within LGBTQIA2S + communities.

Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice.

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)-treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.

Deletion of Growth Hormone Secretagogue Receptor in Kisspeptin Neurons in Female Mice Blocks Diet-Induced Obesity.

The gut peptide, ghrelin, mediates energy homeostasis and reproduction by acting through its receptor, growth hormone secretagogue receptor (GHSR), expressed in hypothalamic neurons in the arcuate (ARC). We have shown 17β-estradiol (E2) increases expression in Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons, enhancing sensitivity to ghrelin. We hypothesized that E2-induced expression augments KNDy sensitivity in a fasting state by elevating ghrelin to disrupt energy expenditure in females.

Chronic stress-induced synaptic changes to corticotropin-releasing factor-signaling in the bed nucleus of the stria terminalis.

The sexually dimorphic bed nucleus of the stria terminalis (BNST) is comprised of several distinct regions, some of which act as a hub for stress-induced changes in neural circuitry and behavior. In rodents, the anterodorsal BNST is especially affected by chronic exposure to stress, which results in alterations to the corticotropin-releasing factor (CRF)-signaling pathway, including CRF receptors and upstream regulators. Stress increases cellular excitability in BNST CRF+ neurons by potentiating miniature excitatory postsynaptic current (mEPSC) amplitude, altering the resting membrane potential, and diminishing M-currents (a voltage-gated K+ current that stabilizes membrane potential).

Centering the Needs of Transgender, Nonbinary, and Gender-Diverse Populations in Neuroendocrine Models of Gender-Affirming Hormone Therapy.

Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens.

Implications of estrogen receptor alpha (ERa) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice.

Previously, organophosphate flame retardants (OPFRs) were found to produce intersecting disruptions of energy homeostasis using an adult mouse model of diet-induced obesity. Using the same mixture consisting of 1 mg/kg/day of each triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate, the current study aimed to identify the role of estrogen receptor alpha (ERα) in OPFR-induced disruption, utilizing ERα knockout (ERαKO) mice fed either a low-fat diet (LFD) or high-fat diet (HFD). Body weight and composition, food intake patterns, glucose and insulin tolerance, circulating peptide hormones, and expression of hypothalamic genes associated with energy homeostasis were measured.

Implications of peroxisome proliferator-activated receptor gamma (PPARY) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice.

Previously, organophosphate flame retardants (OPFRs) were demonstrated to dysregulate homeostatic parameters of energy regulation within an adult mouse model of diet-induced obesity. Using the same OPFR mixture consisting of 1 mg/kg/day of each triphenyl phosphate, tricresyl phosphate, and tris(1,3-dichloro-2-propyl)phosphate, the current study examined the role of peroxisome proliferator-activated receptor gamma (PPARγ) in OPFR-induced disruption by utilizing mice with brain-specific deletion of PPARγ (PPARγKO) fed either a low-fat diet (LFD) or high-fat diet (HFD). Body weight and composition, feeding behavior, glucose and insulin tolerance, circulating peptide hormones, and expression of hypothalamic genes associated with energy homeostasis were recorded.